This proposal, designed to investigate basic immune mechanisms in the human lung, focuses on Immunoglobulin G as a pivotal molecule in host defense of the lower respiratory tract. We are characterizing its function in terms of activity in the four respective gamma chain subclasses. Three lung mechanisms that directly involve specific gamma-chain function are being emphasized: 1) development of opsonic antibody, 2) specific subclass binding to alveolar macrophages which promote phagocytosis and 3) following phagocytosis, release of chemotactic substances from macrophages which initiate the inflammatory process in lung parenchyma. The pattern of IgG subclasses present in respiratory secretions (bronchoalveolar lavage) and serum will be identified for a variety of interstitial lung diseases which have elevated concentrations of IgG in lung secretions or tissue. Progress to date (01-year) on this grant has centered 1) on the development of specific antisera to the gamma-chain subclasses and 2) on characterization of inflammatory mediators (chemotatic factors) released from culture alveolar macrophages. With respect to antisera production, Fc fragments prepared from IgG gamma-chains were used to immune monkeys. Precipitating antisera were raised and final absorptions for immuno-specificity are underway. From in vitro stimulated macrophage cultures, at least two chemotactically active factors have been recovered and purified. The larger factor (10,000 MW) is not a complement fragment nor similar to other known mediators, the smaller factor (1400 MW) is less well characterized but may represent a fragment of the other factor.